scholarly journals Thermodynamics of radicicol binding to human Hsp90 alpha and beta isoforms

2010 ◽  
Vol 152 (1-3) ◽  
pp. 153-163 ◽  
Author(s):  
Asta Zubrienė ◽  
Malgorzata Gutkowska ◽  
Jurgita Matulienė ◽  
Romanas Chaleckis ◽  
Vilma Michailovienė ◽  
...  
Keyword(s):  
Hsp90 Alpha

scholarly journals Severe Hyperthermia Induces Apoptosis Mediated by Caspases Activation and Suppression of Hsp90-alpha Expression in Osteosarcoma Cells

2019 ◽  
Vol 11 (2) ◽  
pp. 167-74
Author(s):  
Mohammed Ali Nashiry ◽  
Gabriele Ruth Anisah Froemming ◽  
Yeap Swee Keong ◽  
Aletza Binti Mohd Ismail ◽  
Aisha Mohd Din ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Heat Shock ◽  
Er Stress ◽  
Therapeutic Potential ◽  
Heat Shock Protein 90 ◽  
Osteosarcoma Cells ◽  
B Cell Leukemia ◽  
Cell Death Mechanisms ◽  
Shock Proteins ◽  
Hsp90 Alpha

BACKGROUND: Hyperthermia is used as an adjuvant treatment to sensitize cancer cells to subsequent radiotheraphy or chemotherapy. The aim of this study was to study the effect of severe hyperthermia on osteosarcoma cells and its underlying causes.METHODS: Short-term (1 h) severe hyperthermia (45°C) was applied to osteoblast-like osteosarcoma cells (MG-63) and the heat shock response and cell death mechanisms were investigated after recovery at 37°C for 72 h.RESULTS: Cell viability was significantly reduced (p<0.05) and apoptosis was significantly induced by severe hyperthermia in MG-63 cells (p<0.001). Caspase 3/7, 4 and 12 activities were significantly increased after 72 h of recovery at 37°C, indicating that severe hyperthermia induced endoplasmic reticulum (ER) stress and apoptosis (p<0.05). Heat shock protein 90 alpha (Hsp90α) was significantly down regulated at the protein level after recovery, in association with apoptosis induction (p<0.01). Additionally, caspase 8 and 9 were activated, possibly as a result of ER stress or other stimuli while, B-cell leukemia 2 family protein (BCL-2) mRNA was down regulated (p<0.01).CONCLUSION: Severe hyperthermia could cause prolonged cell cytotoxicity by inducing apoptosis in association with inhibition of Hsp90α. This indicates the therapeutic potential of severe hyperthermia for the treatment of osteosarcoma.KEYWORDS: hyperthermia, apoptosis, endoplasmic reticulum, stress, heat shock proteins, osteosarcoma

Serum HSP90-Alpha and Oral Squamous Cell Carcinoma : A Prospective Biomarker

2021 ◽  
Vol 28 ◽  
Author(s):  
Muhammad Usman ◽  
Amber Ilyas ◽  
Basir Syed ◽  
Zehra Hashim ◽  
Aftab Ahmed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cancer Patients ◽  
Normal Tissue ◽  
Prognostic Biomarker ◽  
Serum Samples ◽  
Oral Cancer Patients ◽  
Hsp90 Alpha

Aim: Current study aims to perform differential protein expression analysis of serum samples from Oral squamous cell carcinoma (OSCC) patients and healthy controls in search of potential diagnostic and/or prognostic biomarker(s). Objective: OSCC is diagnosed late, resulting in poor survival and high mortality. Identification of non-invasive prognostic biomarker is of utmost importance for early diagnosis and proper management of the disease; hence we used proteomic approach to identify potential biomarkers from serum. Methods: Serum samples (OSCC n=45 and control n=30) were depleted and proteins were separated using 2-D gel electrophoresis followed by identification by mass spectrometric analysis. Gene expression analysis of identified proteins in malignant and normal tissue was also performed to complement proteomics studies. Results: Among differentially expressed proteins, a noteworthy observation was up regulation of Heat shock protein alpha (HSP90α) from serum of oral cancer patients. We also observed elevated levels of Haptoglobin (HP) along with down regulation of Type II keratin cytoskeletal 1(KRT1) and serum Albumin (ALB) in oral cancer patients. Gene expression studies of identified proteins in malignant and normal tissue revealed a similar pattern with the exception of KRT1. We believe that elevated levels of serum HSP90 alpha might be used as a potential biomarker. Conclusion: Our findings suggest the contribution of HSP90 alpha and other identified proteins in oral pathology as pro/anti apoptotic modulators, thus they are being considered as predictive biomarkers.

The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo

1994 ◽  
Vol 14 (2) ◽  
pp. 1459-1464
Author(s):  
Y Minami ◽  
Y Kimura ◽  
H Kawasaki ◽  
K Suzuki ◽  
I Yahara
Keyword(s):  
Amino Acid ◽  
Terminal Region ◽  
Full Length ◽  
Yeast Cells ◽  
Amino Acid Residues ◽  
Haploid Strain ◽  
Carboxy Terminal Region ◽  
Carboxy Terminal ◽  
Hsp90 Alpha

The majority of mouse HSP90 exists as alpha-alpha and beta-beta homodimers. Truncation of the 15-kDa carboxy-terminal region of mouse HSP90 by digestion with the Ca(2+)-dependent protease m-calpain caused dissociation of the dimer. When expressed in a reticulocyte lysate, the full-length human HSP90 alpha formed a dimeric form. A plasmid harboring human HSP90 alpha cDNA was constructed so that the carboxy-terminal 49 amino acid residues were removed when translated in vitro. This carboxy-terminally truncated human HSP90 alpha was found to exist as a monomer. In contrast, loss of the 118 amino acid residues from the amino terminus of human HSP90 alpha did not affect its in vitro dimerization. Introduction of an expression plasmid harboring the full-length human HSP90 alpha complements the lethality caused by the double mutations of two HSP90-related genes, hsp82 and hsc82, in a haploid strain of Saccharomyces cerevisiae. The carboxy-terminally truncated human HSP90 alpha neither formed dimers in yeast cells nor rescued the lethal double mutant.

HSP90 Chaperone – An Important Player in CML: Study At RNA and Protein Level

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4878-4878
Author(s):  
Marketa Zackova ◽  
Tereza Lopotova ◽  
Sylvie Nadvornikova ◽  
Hana Klamova ◽  
Jana Moravcova
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Mrna Expression ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Advanced Disease ◽  
Response To Therapy ◽  
Mrna Levels ◽  
Expression Levels ◽  
Hsp90 Alpha ◽  
Mrna Expression Levels

Abstract Abstract 4878 Chronic myeloid leukemia (CML) is the myeloproliferative disease characterised by presence of BCR-ABL tyrosine kinase, which has been proved to play the basic role in CML ontogenesis. BCR-ABL as well as other kinases active during disease progression (e.g. Src kinase) belong to HSP90 client proteins. It is known, that HSP90 protein is overexpressed in cancer cells and leukemias and is related to therapy resistance in CML cells (Gorre et.al. Blood 2002;100:3041-3044). HSP90 exists in two isoforms: alpha - inducible and beta – constitutively expressed. Taherian et.al. (Biochemistry and Cell Biology, 2008, 86:(1) 37–45) demonstrated that Hsp90α and Hsp90β exhibit similar interactions with cochaperones, but significantly different substrate specificity under stress conditions. Those results reveal both functional similarities and key functional differences between the individual members of this protein family. In our previous study we found high protein expression of total HSP90 in leukocytes of CML patients in advanced disease states and in patients with poor responses (Zackova et.al. EHA 2011). The HSP90 seems to be an indicator of disease deterioration in patients with chronic myeloid leukemia. In the current study, we extended our field of interest on HSP90 isoforms alpha and beta on mRNA level. We aimed to find out possible correlation between protein and mRNA expression levels, as well as between mRNA levels and response to the therapy. We wondered to know whether the monitoring of total HSP90 or its isoforms in CML can early predict the disease deterioration. We tested HSP90 alpha and HSP90 beta mRNA expression levels in patients with various response of CML by real-time RT-PCR method. The mRNA profiles showed high similarity with the data obtained from previous western blot analyses. The analyses showed that high HSP90 levels are associated with poor response to therapy and in advanced disease phases. These levels are probably represented by HSP90-beta isoform (constitutively expressed), which is expressed in higher levels comparing to HSP90 alpha in all samples tested. Expression of HSP90 alpha isoform is much lower while its mRNA expression level highly increases only in blast crisis. Studying both isoformes separately could distinguish various mechanisms in disease progression. The results of this and previous studies suggest HSP90 (on protein and mRNA levels) is an important molecule for studying of prognosis in CML patients. Thus HSP90 appears to be a candidate for novel marker of CML progression. Disclosures: No relevant conflicts of interest to declare.

TAS-116. Second-generation HSP90-alpha/beta inhibitor, Cancer therapy

2018 ◽  
Vol 43 (1) ◽  
pp. 13
Author(s):  
R. Suzuki ◽  
T. Hidehsima ◽  
K.C. Anderson
Keyword(s):  
Cancer Therapy ◽  
Second Generation ◽  
Alpha Beta ◽  
Hsp90 Alpha

scholarly journals The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo.

1994 ◽  
Vol 14 (2) ◽  
pp. 1459-1464 ◽  
Author(s):  
Y Minami ◽  
Y Kimura ◽  
H Kawasaki ◽  
K Suzuki ◽  
I Yahara
Keyword(s):  
Amino Acid ◽  
Terminal Region ◽  
Full Length ◽  
Yeast Cells ◽  
Amino Acid Residues ◽  
Haploid Strain ◽  
Carboxy Terminal Region ◽  
Carboxy Terminal ◽  
Hsp90 Alpha

The majority of mouse HSP90 exists as alpha-alpha and beta-beta homodimers. Truncation of the 15-kDa carboxy-terminal region of mouse HSP90 by digestion with the Ca(2+)-dependent protease m-calpain caused dissociation of the dimer. When expressed in a reticulocyte lysate, the full-length human HSP90 alpha formed a dimeric form. A plasmid harboring human HSP90 alpha cDNA was constructed so that the carboxy-terminal 49 amino acid residues were removed when translated in vitro. This carboxy-terminally truncated human HSP90 alpha was found to exist as a monomer. In contrast, loss of the 118 amino acid residues from the amino terminus of human HSP90 alpha did not affect its in vitro dimerization. Introduction of an expression plasmid harboring the full-length human HSP90 alpha complements the lethality caused by the double mutations of two HSP90-related genes, hsp82 and hsc82, in a haploid strain of Saccharomyces cerevisiae. The carboxy-terminally truncated human HSP90 alpha neither formed dimers in yeast cells nor rescued the lethal double mutant.

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